Online Server Research Articles

Design of a Helicobacter pylori multi-epitope vaccine based on immunoinformatics.

Helicobacter pylori (H. pylori) is an infectious bacterium that colonizes the stomach of approximately half of the global population. It has been classified as a Group I carcinogen by the World Health Organization due to its strong association with an increased incidence of gastric cancer and exacerbation of stomach diseases. The primary treatment for H. pylori infection currently involves triple or quadruple therapy, primarily consisting of antibiotics and proton pump inhibitors. However, the increasing prevalence of antibiotic resistance poses significant challenges to this approach, underscoring the urgent need for an effective vaccine. In this study, a novel multi-epitope H. pylori vaccine was designed using immunoinformatics. The vaccine contains epitopes derived from nine essential proteins. Software tools and online servers were utilized to predict, evaluate, and analyze the physiochemical properties, secondary and tertiary structures, and immunogenicity of the candidate vaccine. These comprehensive assessments ultimately led to the formulation of an optimal design scheme for the vaccine. Through constructing a novel multi-epitope vaccine based on immunoinformatics, this study offers promising prospects and great potential for the prevention of H. pylori infection. This study also provides a reference strategy to develop multi-epitope vaccines for other pathogens.

Computational analysis of Salmalia malabarica (Bombax ceiba) for the management of ulcerative colitis

Bombax ceiba leaf petiole is used as an enema in the management of ulcerative colitis, but its molecular mechanisms are yet to be established. The current study employed gene set enrichment, network pharmacology, and molecular docking studies to infer the phytocompounds from B. ceiba responsible for the modulation of therapeutic targets of UC First, data of phytocompounds present in the leaf petiole were retrieved from the literature and public phytocompounds databases and their druggability and toxicity prediction was performed by MolSoft and AdverPred online servers, respectively. Furthermore, phytocompounds probable proteins were predicted by SwissTargetPrediction, and targets of UC were retrieved from the GeneCards database. A set of genes molecular pathways were identified by the STRING, Kyoto Encyclopedia of Genes and Genomics database, and pathways involved in UC were sorted and their network between compounds, targets, and pathways was constructed by the Cytoscape software. Molecular docking of hub-gene and targets was performed by the POAP pipeline. Out of 10 compounds, 7 (showed druggability in which Rutin scored the highest druglikeness score of 0.91. A total of 2830 genes were identified for UC, of which 39 matched with targets of phytocompounds (total of 297). These 39 targets were involved in 125 pathways, of which 14 were associated with UC mainly VEGF, IL-17, Neurotrophin, JAK-STAT, cAMP, TNF, TGF-beta, and NF-kappa B, MAPK, PI3K-Akt signaling pathway. Among the predicted targets, MAPK3, TNF, and PTGS2 were identified as a hub gene. Rutin scored the lowest binding energy of −7.9 kcal/mol and possessed 22 interactions with PTGS2 and Astragalin and Isoquercitrin were the next lead hit against PTGS2. It has been concluded that the use of B. ceiba leaf petiole could be a valuable source against UC.

An Immunoinformatic-Based In Silico Identification on the Creation of a Multiepitope-Based Vaccination Against the Nipah Virus.

The zoonotic viruses pose significant threats to public health. Nipah virus (NiV) is an emerging virus transmitted from bats to humans. The NiV causes severe encephalitis and acute respiratory distress syndrome, leading to high mortality rates, with fatality rates ranging from 40% to 75%. The first emergence of the disease was found in Malaysia in 1998-1999 and later in Bangladesh, Cambodia, Timor-Leste, Indonesia, Singapore, Papua New Guinea, Vietnam, Thailand, India, and other South and Southeast Asian nations. Currently, no specific vaccines or antiviral drugs are available. The potential advantages of epitope-based vaccines include their ability to elicit specific immune responses while minimizing potential side effects. The epitopes have been identified from the conserved region of viral proteins obtained from the UniProt database. The selection of conserved epitopes involves analyzing the genetic sequences of various viral strains. The present study identified two B cell epitopes, seven cytotoxic T lymphocyte (CTL) epitopes, and seven helper T lymphocyte (HTL) epitope interactions from the NiV proteomic inventory. The antigenic and physiological properties of retrieved protein were analyzed using online servers ToxinPred, VaxiJen v2.0, and AllerTOP. The final vaccine candidate has a total combined coverage range of 80.53%. The tertiary structure of the constructed vaccine was optimized, and its stability was confirmed with the help of molecular simulation. Molecular docking was performed to check the binding affinity and binding energy of the constructed vaccine with TLR-3 and TLR-5. Codon optimization was performed in the constructed vaccine within the Escherichia coli K12 strain, to eliminate the danger of codon bias. However, these findings must require further validation to assess their effectiveness and safety. The development of vaccines and therapeutic approaches for virus infection is an ongoing area of research, and it may take time before effective interventions are available for clinical use.

Design of a WiFi sensor network to identify transmission zones of respiratory diseases through air quality indicators

infants and postoperative patients. While air extraction and droplet filtration systems are effective in containing these viruses, interconnected ventilation ducts can still facilitate virus transmission in areas with lower viral concentration. This study introduces a Wireless Sensor Network based on WiFi technology, designed to monitor crucial environmental variables such as CO2, TVOC, temperature, and humidity, collectively influencing indoor air quality. Moreover, this network connects to an online server, collaborating with subscribers to store historical data. The stored information aids in identifying patterns and high-risk zones associated with the transmission of respiratory diseases. The outcomes demonstrate a comprehensive, adaptable, and scalable WiFi-based Indoor Air Quality sensor network. Employing the publish-subscribe pattern, the MQTT message transport protocol, and open-access platforms like Streamlit, Supabase, and HiveMQ, along with affordable boards and sensors, this solution offers an innovative, scalable, and cost-effective approach to identifying areas at risk of airborne disease transmission. The system's design prioritizes data precision and reliability, making it a valuable addition to indoor air quality monitoring systems.

Evaluation of phenolic and antioxidant profiles of pink Guava peel (Psidium guajava L. cv Arka kiran) during fruit ripening and its in silico Anti SARS-CoV-2 property

Guava (Psidium guajava L.) is a highly nutritious and economically important fruit. Although fruit peel is generally regarded as a waste, researchers believe that the peel of the guava is rich in bioactive constituents, even higher than the fruit's flesh. The present study aimed to estimate phenolic content (total phenolic and total flavonoid) and assess antioxidant properties of guava fruit peel (pink variety, cv Arka kiran) by 2,2-di (4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and Ferric Reducing Antioxidant Potential (FRAP) assays at five different ripening stages (stage 1 to 5). The TPC and TFC assays were performed by Folin-Ciocalteu and aluminium chloride (AlCl3) methods, respectively. The molecular docking experiment between the major phenolic of guava peel, Catechin and the spike protein of SARS-CoV-2 was performed by the Dockthor online server. Results showed that the peel had high phenolic (highest TPC and TFC, 7307.3 mg gallic acid equivalent/g dry weight [DW] and 433.9 mg quercetin equivalent/g DW, respectively) and antioxidant values (highest DPPH, ABTS and FRAP values 4784.8, 206.6 and 2451 mg ascorbic acid equivalent/g DW, respectively) throughout all stages, although there was a gradual decline in the activity at the later stages. Furthermore, it was found that catechin had a strong binding affinity (-7.591 kcal mol-1) with the spike protein, in silico when compared with the control drug ceftazidime (-7.250 kcal mol-1). The overall outcome of our experiemnts revealed that guava peel could be explored for future pharmacological applications through in vivo studies, and the ‘green mixed with the yellow’ stage of ripening is optimum for such studies.

Synthesis, antimicrobial, DFT, and in silico pharmacokinetic profiling of nitroaldol quinoline derivatives: A comprehensive exploration for designing potential oral antibacterial agents targeting DNA-gyrase

This study presents a thorough exploration of the synthesis, biological activities, and molecular properties of a novel series of β-nitroaldol quinoline derivatives (4a-4i). Structural characterization utilized FTIR, 1H NMR, 13C NMR, and mass spectrometry, providing a comprehensive understanding of the synthesized derivatives. Moreover, anti-microbial properties were evaluated using agar disk diffusion assay against five pathogenic strains, including Gram-negative and Gram-positive bacteria, as well as a fungal strain. Notably, compound 4e demonstrated strong anti-fungal and anti-bacterial activities (MIC = 25 µg/ml). A detailed analysis of molecular orbitals, total density of state, vibrational characteristics, global reactivity descriptors, molecular electrostatic potential, topological QTAIM analysis, and molecular docking provided nuanced insights into the reactivity, electronic properties, and potential interactions of the synthesized compounds. These findings contribute valuable information to the design and synthesis of compounds targeting bacterial DNA-gyrase. Furthermore, in silico predictions using the SwissADME online server indicated that all compounds comply with Lipinski's rule of five, suggesting their potential as orally active drugs. The compounds demonstrated commendable water solubility, passed various filters, and exhibited bioavailability scores, indicating promising oral bioavailability. The percentage of oral absorption ranged from 75.39% to 78.58%, signifying high permeability. Computational analysis of pharmacokinetic parameters revealed favorable characteristics, including gastrointestinal absorption and minimal inhibitory effects on specific enzymes.

DeepProSite: structure-aware protein binding site prediction using ESMFold and pretrained language model.

Identifying the functional sites of a protein, such as the binding sites of proteins, peptides, or other biological components, is crucial for understanding related biological processes and drug design. However, existing sequence-based methods have limited predictive accuracy, as they only consider sequence-adjacent contextual features and lack structural information. In this study, DeepProSite is presented as a new framework for identifying protein binding site that utilizes protein structure and sequence information. DeepProSite first generates protein structures from ESMFold and sequence representations from pretrained language models. It then uses Graph Transformer and formulates binding site predictions as graph node classifications. In predicting protein-protein/peptide binding sites, DeepProSite outperforms state-of-the-art sequence- and structure-based methods on most metrics. Moreover, DeepProSite maintains its performance when predicting unbound structures, in contrast to competing structure-based prediction methods. DeepProSite is also extended to the prediction of binding sites for nucleic acids and other ligands, verifying its generalization capability. Finally, an online server for predicting multiple types of residue is established as the implementation of the proposed DeepProSite. The datasets and source codes can be accessed at https://github.com/WeiLab-Biology/DeepProSite. The proposed DeepProSite can be accessed at https://inner.wei-group.net/DeepProSite/.

Effects of Acute and Repeated Dose Toxicity Profiling of Chelidonic Acid in Rats: in Silico and in Vivo Evidence.

Chelidonic acid is a phytoconstituent found in rhizomes of the perennial plant celandine. The current study aims to evaluate the acute and repeated dose oral toxicity study of chelidonic acid as per the OECD guidelines 425 and 407. The pharmacokinetic and toxicity profile of chelidonic acid was predicted using online servers and tools. A single dose of chelidonic acid (2000 mg/kg) was administered to female Wistar rats in an acute toxicity study, and the animals were monitored for 14 days. We studied the toxicity profile of chelidonic acid at 10, 20, and 40 mg/kg doses in Wistar rats for repeated dose toxicity (28 days). Clinical biochemistry, haematological, and urine parameters were estimated. A gross necropsy and histopathology were performed. A single oral dose of chelidonic acid (2000 mg/kg) showed no signs of toxicity or mortality. The Administration of chelidonic acid showed no significant alterations in haematological, biochemical, and urine parameters. The histopathology showed normal structure and architecture in all the vital organs. A gross necropsy of vital organs showed no signs of toxicity. The chelidonic acid was found to be safe at all selected dose levels in the acute and repeated dose toxicity study in rats.

Pharmacokinetics, dynamics, toxicology and molecular docking of bioactive alkaloid vasicine from Adhatoda vasica: a promising toxin binder against aflatoxin B1 and ochratoxin A

Vasicine form Adhatoda vasica was investigated in the management of aflatoxicosis and ochratoxicosis by in silico molecular docking approach. The computational analysis was carried out using Discovery Studio Autodock 4.0 tool. ADME (Absorption, Distribution, Metabolism and Excretion), pharmacodynamic and toxicity studies were also carried out using Swiss ADME and PASS online server respectively. The standard drug compound used was silymarin and the structure were retrieved from the protein data bank for both the test compound vasicine and the standard drug. Vasicine interacted with Aflatoxin B1 at 10 different poses and the maximum dock score was found to be 83.04 and the binding energy was -37.54kcal/mol. Silymarin interacted with Aflatoxin B1 at 10 different poses and the maximum dock score was found to be 143.578 binding energy was -67.32 kcal/mol. Vasicine interacted with Ochratoxin A at 10 different poses and the maximum dock score was found to be 73.75 and the binding energy was -56.20 kcal/mol. Silymarin interacted with Ochratoxin A at 10 different poses and the maximum dock score was found to be 89.23 binding energy was -98.86kcal/mol. The compounds possess good gastro intestinal absorption with antioxidant property and exhibits minimum adverse effects. The obtained results support the toxin mitigating potential of the test compound with minimum adverse effects and hence vasicine can be regarded as a potential toxin binder of aflatoxin B1 and ochratoxin A wherein it can be implemented for alleviating aflatoxicosis and ochratoxicosis.

Synthesis, characterization, biological activity and computation-based efficacy of cobalt(II) complexes of biphenyl-2-ol against SARS-CoV-2 virus

Cobalt(II) complexes of biphenyl-2-ol of composition, CoCl2-n(OC6H4C6H5-2)n(H2O)4 (where n = 1 or 2), were prepared by reacting cobaltous(II) chloride with equi- and bimolar ratios of sodium salt of biphenyl-2-ol. The structural characterization of the synthesized complexes was accomplished by NMR, FTIR, thermogravimetry (TGA), high resolution mass spectroscopy (HRMS), electronic spectroscopic techniques coupled with density functional theory (DFT). The stability of the complexes in different pH media of solvent was studied. Chemical reactivity parameters of the newly synthesized complexes, computed using DFT, indicated greater reactivity of complex 2 over complex 1 and free ligand as indicated by its low HOMO-LUMO energy gap corresponding to 1.71 eV. Molecular docking (MD) studies were carried out in order to study the binding affinities between amino acid residues of DNA duplex (PDB ID: 1BNA) and SARS-CoV-2 (PDB ID: 7T9K) with newly synthesized complexes. Complex 2 has shown promising antivirus behaviour with an inhibition constant value of 0.0423 µmol−1 with amino acid residues of SARS-CoV-2 virus. Toxicity of the complexes was predicted using ProTox-II online server. Antibacterial studies have indicated the complexes to exhibit greater efficacy than the free ligand, while the antioxidant activities have suggested them to display enhanced antioxidant behaviour as compared to reference compounds. Communicated by Ramaswamy H. Sarma

Computational biology of antibody epitope, tunnels and pores analysis of protein glutathione S-transferase P, and quantum mechanics

Different tissues of various plants contain allelochemicals such as phenolics, flavonoids, etc., which exhibit antioxidants and protect the plants from harmful infections. The widespread group of plant allelochemicals in the ecosystem is phenolic compounds. They are substances composed of an aromatic hydrocarbon group and a hydroxyl group. The 3-Hydroxyflavone skeleton of flavonol has a phenolic and a hydroxyl substitution. A comparison of experimental and calculated data of FT-IR and Raman was studied for the vibrational assessment of these allelochemicals. PES scan and molecular geometry analysis are done for the conformation of the 3-Hydroxyflavone ligand. 3-Hydroxyflavone is docked with the three proteins of Homo sapiens such as Prothrombin with 622 amino acids synthesized in the liver, human neutrophils found within intracellular granules with 467 amino acids, Glutathione S-transferase P is produced from exogenous xenobiotics with 210 amino acids. The active site residues by using the Prothrombin (1A2C), Neutrophil collagenase (1A86), Glutathione S-transferase P(18 GS) protein with ligand 3-Hydroxyflavone, fair binding affinity was found for the Glutathione S-transferase P (18 GS). The MOLE online server web interface's ability to see and analyze tunnels and pores allows for simple, online interaction with bio-macromolecule investigation. The automatic transmembrane channel calculation on the MOLE web generates the quickest list of ligands for transport analysis and tunnel identification. Pore-forming proteins (PFPs) are recognized as crucial agents in immunity and infection. They target membranes by opening channels through them. ElliPro is thought to be a potentially effective method for identifying antibody epitopes in protein antigens. Molecular dynamics result the general time-dependent structural deviation/degree of similarity among the structures that the trajectory records. The epitope technique sought to examine the effectiveness of its web tool on linear and discontinuous epitopes known from the structures of antibodies of 18 GS with 3-Hydroxyflavone complexes and find effective scores.

In silico molecular docking studies of 2, 4 and 2, 6-di-tert-butylphenol against NAGK and SPP1 proteins to recuperate rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that primarily affects the synovial joints. It is connected to progressive disability, early death and socioeconomic burdens. So, there is an urgent need to develop novel drugs that effectively treat patients at each stage of disease progression. N-acetylglucosamine kinase (NAGK) and secreted phosphoprotein 1(SPP1) are two attractive drug targets for RA. NAGK protein converts endogenous N-acetyl-D-glucosamine (GlcNAc) into GlcNAc 6-phosphate. GlcNAc has suppressive effects on experimental RA in mouse models. SPP1 stimulates the synthesis of a key proinflammatory cytokine implicated in the pathogenesis of RA. In order to design new drug candidates, crystal structure of human NAGK (PDB Id: 2CH5) was retrieved from the protein data bank. Amino acid sequence of SPP1 (Uniprot Id: P10451) was retrieved from uniprot database and modeled by the Phyre2 server. Computed SPP1 model energy was minimized using the YASARA energy minimization server and validated by the Ramachandran plot and the ProSA-web error-detection tool. 2, 4-Di-tert-butylphenol and 2, 6-Di-Tert-butylphenol are known compound isolates from bark extract of Schleichera oleosa having anti-arthritic and anti-inflammatory activities as accessed by PASS online server. These compounds were docked against active site of NAGK and SPP1 proteins using MTiAutoDock server. The binding affinity of these compounds against NAGK and SPP1 proteins ranges from -6.12 to -7.17 kcal/mol. The findings of this study will open the way for the development of herbal remedies for rheumatoid arthritis based on the Schleichera oleosa plant, potentially leading to the development of novel drugs.

A Nomogram Model for Post-Intubation Hypotension in Patients with Severe Pneumonia in the Emergency Department.

Post-intubation hypotension (PIH) frequently occurs in the management of critically ill patients and is associated with prognosis. The study aimed to construct a prediction model for PIH events by analyzing risk factors in patients with severe pneumonia in the emergency department. We retrospectively enrolled 572 patients with severe pneumonia diagnosed in the emergency department of West China Hospital of Sichuan University. Five hundred patients with severe pneumonia who underwent endotracheal intubation were included in the study. All patients were randomized according to 7:3 and divided into a training cohort (n=351) and a validation cohort (n=149). Risk factors for PIH were analyzed using Least Absolute Shrinkage and Selection Operator (LASSO) and multivariable logistic regression. Calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis were applied to assess the predictive model's fitness, discrimination, and clinical utility. A total of 500 patients with severe pneumonia who underwent endotracheal intubation were enrolled in this study, and PIH occurred in 234 (46.8%) of these patients. Age, heart rate, systolic blood pressure, chronic obstructive pulmonary disease, acute physiology and chronic health evaluation II score, and induction agent use were identified as significant risk factors for the occurrence of PIH. Additionally, the body mass index was the opposite of the above. The area under the ROC curve (AUC) for the model was 0.856 (95% CI, 0.818-0.894) in the training cohort and 0.849 (95% CI, 0.788-0.910) in the validation cohort. The nomogram model was validated and demonstrated good calibration and high net clinical benefit. Finally, to facilitate application by clinicians, an online server has been set up which can be accessed free of charge via the website https://chinahospitals.shinyapps.io/DynNomapp/. The nomogram is used for individualized prediction of patients with severe pneumonia prior to intubation and is simple to perform with high clinical value.

A high-resolution haplotype-resolved Reference panel constructed from the China Kadoorie Biobank Study.

Precisionmedicine depends on high-accuracy individual-level genotype data. However, the whole-genome sequencing (WGS) is still not suitable for gigantic studies due to budget constraints. It is particularly important to construct highly accurate haplotype reference panel for genotype imputation. In this study, we used 10000 samples with medium-depth WGS to construct a reference panel that wenamed theCKB reference panel. By imputing microarray datasets, it showed that the CKB panel outperformed compared panels in terms of both the number of well-imputed variants and imputation accuracy. In addition, we have completed the imputation of 100 706 microarrays with the CKB panel, and the after-imputed data is the hitherto largest whole genome data of the Chinese population. Furthermore, in the GWAS analysis of real phenotype height, the number of tested SNPs tripled and the number of significant SNPs doubled after imputation. Finally, we developed an online server for offering free genotype imputation service based on the CKB reference panel (https://db.cngb.org/imputation/). We believe that the CKB panel is of great value for imputing microarray or low-coverage genotype data of Chinese population, and potentially mixed populations. The imputation-completed 100 706 microarray data are enormous and precious resources of population genetic studies for complex traits and diseases.

Immunoinformatics Approach for the Design of Chimeric Vaccine Against Whitmore Disease

Purpose: Multidrug-resistant Burkholderia pseudomallei is associated with significant morbidity and mortality. Hence, there is a requirement for a vaccine for this pathogen. Using subtractive proteomics and reverse vaccinology approaches, we have designed a chimeric multiepitope vaccine against the pathogen in the present study. Methods: Twenty-one non-redundant pathogen proteomes were mined using a subtractive proteomics strategy. Out of these, by various analyses, we found proteins that were non-homologous to humans, essential, and virulent. BLASTp against the PDB database and Pocket druggability analysis yielded nine proteins whose 3D structure is available and are druggable. Four proteins that could be candidates for vaccines were identified by subcellular localization and antigenicity prediction, and they could be used in reverse vaccinology methods to create a chimeric multiepitope vaccine. Results: Using online resources and servers, MHC class I, II, and B cell epitopes were identified. The predicted epitopes were selected based on analysis of toxicity, solubility, allergenicity, and hydrophilicity. These predicted epitopes, which were immunogenic, were used for the construction of a multivalent chimeric vaccine. The epitopes, adjuvants, linkers, and PADRE amino acid sequences were employed to create the vaccine. Shortlisted vaccine constructs also interact with the HLA allele and TLR4, as evident from docking and molecular dynamics simulation. Thus, vaccine construct V1 can elicit an immune response against Burkholderia pseudomallei. Conclusion: The availability of the proteome of B. pseudomallei has made this study possible through the usage of various in silico approaches. We could shortlist vaccine targets using subtractive proteomics and then construct chimeric vaccines using reverse vaccinology and immunoinformatics approaches.

Could Unfold Protein Response Pathway Proteins be a Missing Link in Neuropathic Pain and Alzheimer’s Disease Etiology? — Findings from Computational Studies

Background: Neurodegenerative diseases, including Alzheimer’s disease, are characterized by progressive neuronal cell loss and nervous system damage. Neuropathic pain, resulting from traumatic injury to sensory nerves, is closely associated with these neurodegenerative conditions. Endoplasmic reticulum (ER) stress, arising from protein misfolding or accumulation of unfolded proteins, plays a crucial role in maintaining cellular homeostasis through the activation of the unfolded protein response (UPR). Interestingly, the ER stress pathway has emerged as a potential link between neuropathic pain and Alzheimer’s disease. To investigate this link, we selected specific drugs with known mechanisms of action: GSK2606414, an EIF-2[Formula: see text] phosphorylation inhibitor, Valsartan, which down-regulates ER stress-related proteins, Gemigliptin, known to decrease GRP78 expression, and Melatonin, shown to reduce ATF6 mRNA and protein levels. Additionally, Vemurafenib and Obatoclax were chosen as kinase and Bcl2 inhibitors, respectively. Drug selection was based on data from DrugBank and literature, with their structures obtained from the PubChem database. Main methodologies: Our research aims to identify potential therapeutic targets bridging neuropathic pain and Alzheimer’s disease. Using AutoDock v4.2.6, we conducted molecular docking studies, revealing promising drug–target interactions. We further performed molecular dynamic (MD) simulations for 100 ns using the WEBGRO online server to assess drug-target stability. Additionally, we employed Lipinski screening via the SwissADME web server, assessing pharmacokinetic properties and toxicity. Results: Except for ATF4 (with Metformin), all targets showed favorable affinity toward Obatoclax, with binding energies ranging from −5.32 to −7.48 kcal/mol. The XBP1–Obatoclax complex stability is evaluated using MD simulation. The ADMET screening results indicated that the drugs displayed good intestinal absorption (above 30%), making them suitable for oral administration. Importantly, these drugs showed no inhibitory effects against CYP2D6 isozymes expressed in the CNS. Future perspective: Our in silico findings provide valuable evidence and potential leads for further evaluation and confirmation through in vitro research. The data generated from this study may contribute to the development of novel therapeutics targeting both neuropathic pain and Alzheimer’s disease, offering new hope for patients suffering from these debilitating conditions.

MHapBrowser: a comprehensive database for visualization and analysis of DNA methylation haplotypes.

DNA methylation acts as a vital epigenetic regulatory mechanism involved in controlling gene expression. Advances in sequencing technologies have enabled characterization of methylation patterns at single-base resolution using bisulfite sequencing approaches. However, existing methylation databases have primarily focused on mean methylation levels, overlooking phased methylation patterns. The methylation status of CpGs on individual sequencing reads represents discrete DNA methylation haplotypes (mHaps). Here, we present mHapBrowser, a comprehensive database for visualizing and analyzing mHaps. We systematically processed data of diverse tissues in human, mouseand rat from public repositories, generating mHap format files for 6366 samples. mHapBrowser enables users to visualize eight mHap metrics across the genome through an integrated WashU Epigenome Browser. It also provides an online server for comparing mHap patterns across samples. Additionally, mHap files for all samples can be downloaded to facilitate local processing using downstream analysis toolkits. The utilities of mHapBrowser were demonstrated through three case studies: (i) mHap patterns are associated with gene expression; (ii) changes in mHap patterns independent of mean methylation correlate with differential expression between lung cancer subtypes; and (iii) the mHap metric MHL outperforms mean methylation for classifying tumor and normal samples from cell-free DNA. The database is freely accessible athttp://mhap.sibcb.ac.cn/.

Bacillus changyiensis sp. nov., isolated from coastal sediment.

Two Gram-stain-positive, facultatively anaerobic, motile, endospore-forming, rod-shaped bacteria, designated CLL-3-40T and CLL-7-23, were isolated from coastal sediment sampled in Changyi, Shandong Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that these strains were related to the genus Bacillus and close to six type strains of species within the Bacillus licheniformis group. In phenotypic characterization tests, strain CLL-3-40T could grow at 15-50 °C (optimum, 37 °C) and in media with pH 5-9 (optimum pH 7.0), and tolerate up to 12 % (w/v) NaCl. The fermentation broth supernatant extracted by ethyl acetate of strain CLL-3-40T could inhibit aquaculture pathogenic vibrios. The predominant cellular fatty acids of strain CLL-3-40T were anteiso-C15 : 0 (30.7 %) and iso-C15 : 0 (31.5 %); the peptidoglycan from cell-wall contained meso-diaminopimelic acid; the predominant quinone was menaquinone 7; and the major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, an unidentified glycolipid and two unidentified phospholipids. The digital DNA-DNA hybridization values and average nucleotide identities among strains CLL-3-40T and CLL-7-23 and their close type strains were less than 21.9 and 48.4 %, respectively, thereby indicating that strain CLL-3-40T should represent a novel species of the genus Bacillus. The genomic DNA G+C contents were 38.4 mol% in strain CLL-3-40T and 38.3 mol% in strain CLL-7-23. The 12 biosynthetic gene clusters of strain CLL-3-40T were predicted based on results from the online server antiSMASH. Based upon the consensus of phenotypic and genotypic results, strain CLL-3-40T should be classified as representing a novel species of the genus Bacillus, for which the name Bacillus changyiensis sp. nov. is proposed. The type strain is CLL-3-40T (= MCCC 1A14857T=JCM 35755T).

In silico approach of bioactive molecule chitosan 501.1 kDa from snail shell as antioxidant and inhibitor of the keap1-nrf2 protein-protein interaction

Background: ROS are created when high levels of oxidative stress occur due to hypercholesterolemia. Nuclear Factor Erythroid 2-related factor (NRF2) controls the expression of antioxidant genes. Kelch-like ECH-associated protein 1 (KEAP1) therapy degrades NRF2. Chitosan 501.1 kDa from snail shells contains bioactive chemicals that can induce NRF2 activity. Objective: To evaluate the potential antioxidant activity of the bioactive compound in Mw 501.1 kDa chitosan by targeting KEAP1 and NRF2 proteins in-silico. Method: The 3D structures of the bioactive compounds chitosan and control 51M were derived from the PubChem database, and the proteins were derived from the RCSB PDB. The biological activity of chitosan bioactive compounds was predicted using the PASS Online server. Molecular docking was performed using Hex 8.0.0 Cuda with Shape+Electro+DARS and visualised with Discovery Studio. The biological activity of chitosan compounds was predicted as lipotropic and antioxidant. Result: The discovery of the bioactive compound chitosan 501.1 kDa interacted strongly with KEAP1. The bioactive compound chitosan also inhibited KEAP1 through residues GLN75 and LEU84 at the 51M-KEAP1 interaction. Conclusion: The bioactive compound chitosan 501.1 kDa could inhibit the interaction of KEAP1-NRF2 proteins so that NRF2 could transcribe antioxidant genes. Therefore, may serve as a suitable alternative.

Computational exploration and design of a multi-epitopes vaccine construct against Chlamydia psittaci

Chlamydia psittaci is an intracellular pathogen and causes variety of deadly infections in humans. Antibiotics are effective against C. psittaci however high percentage of resistant strains have been reported in recent times. As there is no licensed vaccine, we used in-silico techniques to design a multi-epitopes vaccine against C. psittaci. Following a step-wise protocol, the proteome of available 26 strains was retrieved and filtered for subcellular localized proteins. Five proteins were selected (2 extracellular and 3 outer membrane) and were further analyzed for B-cell and T-cell epitopes prediction. Epitopes were further checked for antigenicity, solubility, stability, toxigenicity, allergenicity, and adhesive properties. Filtered epitopes were linked via linkers and the 3D structure of the designed vaccine construct was predicted. Binding of the designed vaccine with immune receptors: MHC-I, MHC-II, and TLR-4 was analyzed, which resulted in docking energy scores of −4.37 kcal/mol, −0.20 kcal/mol and −22.38 kcal/mol, respectively. Further, the docked complexes showed stable dynamics with a maximum value of vaccine-MHC-I complex (7.8 Å), vaccine-MHC-II complex (6.2 Å) and vaccine-TLR4 complex (5.2 Å). As per the results, the designed vaccine construct reported robust immune responses to protect the host against C. psittaci infections. In the study, the C. psittaci proteomes were considered in pan-genome analysis to extract core proteins. The pan-genome analysis was conducted using bacterial pan-genome analysis (BPGA) software. The core proteins were checked further for non-redundant proteins using a CD-Hit server. Surface localized proteins were investigated using PSORTb v 3.0. The surface proteins were BLASTp against Virulence Factor Data Base (VFDB) to predict virulent factors. Antigenicity prediction of the shortlisted proteins was further done using VAXIGEN v 2.0. The epitope mapping was done using the immune epitope database (IEDB). A multi-epitopes vaccine was built and a 3D structure was generated using 3Dprot online server. The docking analysis of the designed vaccine with immune receptors was carried out using PATCHDOCK. Molecular dynamics and post-simulation analyses were carried out using AMBER v20 to decipher the dynamics stability and intermolecular binding energies of the docked complexes. Communicated by Ramaswamy H. Sarma